Vascular endothelial growth factor can substitute for macrophage colony-stimulating factor in the support of osteoclastic bone resorption.
Vascular endothelial growth factor can substitute for macrophage colony-stimulating factor in the support of osteoclastic bone resorption.
复制标题
血管内皮生长因子可以替代巨噬细胞集落刺激因子来支持破骨细胞骨吸收。
DOI：
10.1084/jem.190.2.293
复制
发表时间：
1999-07-19
影响因子：
15.3
通讯作者：
Kodama, H
中科院分区：
文献类型：
--
作者：
Niida, S;Kaku, M;Amano, H;Yoshida, H;Kataoka, H;Nishikawa, S;Tanne, K;Maeda, N;Nishikawa, S;Kodama, H
我们以前证明，单次注射重组人巨噬细胞集落刺激因子（rhM-CSF）是足够的破骨细胞的招聘和生存骨硬化（OP/OP）小鼠与破骨细胞的缺陷导致的突变M-CSF基因。在这项研究中，我们表明，单次注射重组人血管内皮生长因子（rhVEGF）可以类似地诱导破骨细胞招募OP/OP小鼠。破骨细胞主要表达VEGF受体1（VEGFR-1），重组人胎盘生长因子1对破骨细胞募集的活性与rhVEGF相当，表明VEGF信号通过VEGFR-1介导。rhM-CSF诱导的破骨细胞在注射VEGFR-1/Fc嵌合蛋白后死亡，其作用被同时注射rhM-CSF废除。由rhM-CSF或内源性VEGF支持的破骨细胞在骨吸收活性方面没有显着差异。OP/OP小鼠经历了与年龄相关的骨硬化消退，伴随着破骨细胞数量的增加。大多数破骨细胞在注射抗VEGF抗体后消失，表明内源性产生的VEGF是突变小鼠中破骨细胞出现的原因。此外，rhVEGF取代rhM-CSF在体外破骨细胞分化的支持。这些结果表明，M-CSF和VEGF在支持骨细胞骨吸收方面具有重叠的功能。
We demonstrated previously that a single injection of recombinant human macrophage colony-stimulating factor (rhM-CSF) is sufficient for osteoclast recruitment and survival in osteopetrotic (op/op) mice with a deficiency in osteoclasts resulting from a mutation in M-CSF gene. In this study, we show that a single injection of recombinant human vascular endothelial growth factor (rhVEGF) can similarly induce osteoclast recruitment in op/op mice. Osteoclasts predominantly expressed VEGF receptor 1 (VEGFR-1), and activity of recombinant human placenta growth factor 1 on osteoclast recruitment was comparable to that of rhVEGF, showing that the VEGF signal is mediated through VEGFR-1. The rhM-CSF–induced osteoclasts died after injections of VEGFR-1/Fc chimeric protein, and its effect was abrogated by concomitant injections of rhM-CSF. Osteoclasts supported by rhM-CSF or endogenous VEGF showed no significant difference in the bone-resorbing activity. op/op mice undergo an age-related resolution of osteopetrosis accompanied by an increase in osteoclast number. Most of the osteoclasts disappeared after injections of anti-VEGF antibody, demonstrating that endogenously produced VEGF is responsible for the appearance of osteoclasts in the mutant mice. In addition, rhVEGF replaced rhM-CSF in the support of in vitro osteoclast differentiation. These results demonstrate that M-CSF and VEGF have overlapping functions in the support of osteoclastic bone resorption.